An experienced team of investigators from Cornell University's Weill Medical College and Columbia University are proposing a set of new research projects and core activities for a 10-year-old NIDA-funded MULTI-ETHNIC DRUG ABUSE PREVENTION CENTER (MDAPRC). This application has grown out of a longstanding collaborative relationship between the investigators representing the participating institutions and their recognized need for feasible and efficacious interventions designed to prevent drug abuse and reduce avoidable morbidity and mortality in multi-ethnic populations. The structure of the Center consists of two core divisions and four research projects. The functions of the adminstrative core will include administration, training, dissemination, and community liaisons. The Information Management, statistics, and Evaluation core will deal with data management and evaluation. The work of the Center is conceptualized in stages, with the focus of work during the first 10 years of funding on African-American and Hispanic-American adolescents. During the next 5-year funding period, the research of the center will focus more broadly on multi-ethnic youth with an emphasis on issues critical to enhancing the science and practice of prevention. Through a set of well-integrated studies, the proposed research will address issues related to optimizing the effectiveness of school-based prevention through an increased understanding of mediating mechanisms and factors associated with implementation fidelity, adaptation, and cost / benefits. More specifically, this research is designed to provide important new scientific knowledge concerning (1) the impact of enhanced implementation fidelity on the effectiveness of school-based prevention (Project by Botvin), (2) key factors associated with fidelity and adaptation of school-based prevention (Project by Schinke), (3) the mediating role of social / psychological factors on the etiology and prevention of drug abuse (Project by Griffin), and (4) the mediating role of physiologic factors such as pubertal development and stress reactivity on youth drug abuse (Project by Graber). In sum, the work being proposed addresses major gaps in prevention science related to the etiology and prevention of drug abuse in multi-ethnic youth and is designed to provide vitally important knowledge required for improving prevention theory and optimizing the effectiveness and sustainability of evidence-based prevention when taken to scale in real-world settings.